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Physiology is vital to give us an understanding of the normal functioning of the body. This knowledge can help us to maintain health in the people we live and work with. Sometimes however, as a result of trauma, disease or degeneration, the body fails to function normally. This means that, by definition, the function has become abnormal. Abnormal body function is termed pathophysiology. An understanding of normal and abnormal body function is necessary if we are to understand what treatments are indicated in a particular situation. This means physiology, pathophysiology and patient management all interlink. Theory will then inform and provide rationales for interventions. The focus of this text is abnormal function, but this must be considered in the context of physiology and clinical practice. If we understand this linking and interdependence, we can use our knowledge of theory and practice to directly benefit patient care.
This book is intended to be a teaching aid for people who want to understand the causes, pathophysiological changes and clinical features seen in disease processes. Treatment principles are also discussed and should naturally follow on from an understanding of the abnormal processes involved. The topics I have chosen for inclusion in the text are generally those which are most common or illustrate general principles of pathophysiology. My hope is that this book will allow you to understand what is happening to your patients more fully, and that this knowledge will inform practise. Also, I hope it will give you the necessary basic understanding required to comprehend the more detailed texts you will need to gain knowledge about the specific disorders you encounter.
Campbell's Physiology and Pathophysiology books are the only text books that are supported by multinational research of effectiveness, read the full research report using the link below to Sage Open academic publishing.
CHAPTER 1 Nature and Aetiology of Disease - Physiology is the study of normal body function and anatomy is the study of body structure, (ology simply means ‘the study of’). Pathology is the study of disease, involving examination of abnormal structure and function. Pathophysiology is the study of abnormal body function, in disease states, and after trauma. Histology and cytology are the study of tissues and cells respectively. Histopathology and cytopathology are therefore the study of abnormal tissues and cells. Disease literally means any state of not being at ease, there is ‘dis-ease’. This definition could include the effects of trauma, as well as disease processes. In practice we tend to use the term disease to refer to abnormal processes occurring within the body and the way in which these manifest in the individual. Pathogenesis is the process whereby the disordered disease state is produced in the body after the causative factor has been introduced.
CHAPTER 2 Neoplasia – Neoplasia is a general term which means ‘new growth’. In normal physiology there are mechanisms which regulate cell division and the generation of new tissues. If these physiological mechanisms fail for any reason, cells may then multiply at an increased rate. This will result in the presence of a greater number of cells. These cells take up space and usually form lumps which are called tumours. In leukaemia there is an uncontrolled growth of cells from the bone marrow. These do not form tumours, as the excess numbers of abnormal cells enter the blood. In either case when the increased numbers of cells present are malignant, the condition is described as cancer. Cancer is not a single disease. Over 200 different forms of cancer are recognised, depending on the primary site of the malignancy.
CHAPTER 3 Infectious Disease - It has been estimated by the world health organization (WHO) that infectious diseases cause 25% of human deaths worldwide and up to 63% of deaths in children under the age of 4 years. Most of these premature deaths are caused by six major killers. In order of the number of deaths caused these infections are; pneumonia, HIV/AIDS, diarrhoeal diseases, tuberculosis, malaria and measles. The challenge is that all of these major causes of infective deaths can be prevented or treated. This is particularly important as the majority of these preventable deaths occur in our children and young adults. This chapter aims to give the foundational information needed for you to start combating the scourge of infectious disease.
CHAPTER 4 Disorders of Immunity - HIV is a massive global health problem which predominantly affects poorer and developing countries. In sub-Saharan Africa the prevalence may be up to 25% of the total population. Unfortunately, many Asian countries, (e.g. India, Thailand and China) are now experiencing significant problems with the infection. However, effective health education programmes in Cambodia have largely contained the epidemic. Incidence is also increasing in Eastern Europe. As the disease is most commonly sexually transmitted, it often affects young adults. Young adults therefore become sick and die in large numbers, so are unable to work and look after their children effectively. This means the condition has the potential to do massive harm to the social and economic well-being of individuals and nations. In many poor countries, prostitution is a big problem, in India and Africa for example, there are millions of prostitutes. Women (and young men) are often forced into prostitution by criminals who organise human slavery. Poverty also forces many to become prostitutes. The problem can be self-perpetuating; girls orphaned by AIDS may be forced into prostitution to support other children in the family. As health care workers, we know our own communities best, the question is what are we able, and prepared, to do to help this situation?
CHAPTER 5 Disorders of Arteries - There are two common disorders of arteries, arteriosclerosis and atherosclerosis. Arteriosclerosis describes a thickening and hardening (sclerosis means hardening) of arterial walls which mostly affects the walls of the small arteries and arterioles. Arteriolosclerosis is a specific term which describes hardening of the arterioles. As the walls of a vessel thicken, the lumen becomes narrowed resulting in reduced perfusion of the tissues with blood. Hardening also causes the arterial walls to become inelastic. This reduces the ability of the vessel to expand and contract with the pulse which further reduces the efficiency of local perfusion, making the ischaemia worse.
CHAPTER 6 Disorders of Veins - A vein can usefully be defined as any vessel which carries blood towards the heart; this includes systemic veins draining blood back into the right atrium and pulmonary veins transporting blood into the left atrium. An essential area of knowledge for all health care workers is venothromboembolism (VTE). Despite being life threatening, VTE is common and in developed countries is the leading cause of preventable deaths in hospital patients. In VTE a thrombus forms in a vein and then embolises into the venous circulation. It is useful to consider this disorder under the headings of deep venous thrombosis and pulmonary embolism.
CHAPTER 7 Shock - Shock is a much-misused term that is frequently applied to mean a fright or used to describe the psychological effects of trauma. This is not the correct clinical use of the term and health care professionals should use the word shock in a strict sense. Shock describes a state of circulatory failure when the circulation of blood around the body is reduced to such an extent that body tissues are embarrassed or damaged as a result. Tissue embarrassment is caused by factors which may compromise normal function, the principle ones being reduced delivery of oxygen and nutrients and the accumulation of waste products of metabolism. A possible definition of shock is ‘a state with significant reduction in systemic tissue perfusion, resulting in decreased delivery of oxygen and reduced removal of metabolic waste products, leading to tissue injury’. In shock the blood supply and so the oxygen delivery to the tissues of the body are insufficient to meet the metabolic demands of the tissues. In all forms of shock low blood pressure will develop in time. However, this is a sinister development in the progression of shock and the organs and tissues of the body may be seriously hypoperfused before blood pressure starts to fall. This means that the development of shock should be recognised at an early stage, preferably before blood pressure starts to fall. Shock is not a specific disease but can complicate many conditions caused by trauma or disease.
CHAPTER 8 Haemorrhage - As blood is only supposed to be found within the circulatory system, that is within the heart and blood vessels, it follows that haemorrhage is caused by damage to blood vessels. This damage allows bloodto leak out causing bleeding. Haemorrhage is just another word for bleeding. In arterial haemorrhage, the pressure of blood in arteries is high, a cut artery may lose blood rapidly. Initially there will be loss of pulsating, bright red blood. Pulsation means the blood comes out in spurts, with the normal arterial pulses. Fortunately, a cut artery will undergo reflex constriction to reduce blood loss. This may give rise to the presence of bright red oxygenated arterial blood in a wound without obvious pulsation. Venous haemorrhage gives rise to a steady stream of dark red blood. The loss is steady as venous blood does not undergo the pressure changes found in arteries. Venous blood is relatively deoxygenated so is dark red. Capillary haemorrhage often takes the form of oozing from a wound surface. Another presentation of capillary haemorrhage is a bruise (correctly termed a contusion). These develop when there is an accumulation of blood in the tissue spaces. Contusions often result from capillary haemorrhage caused by blunt trauma.
CHAPTER 9 Cardiac Disorders - CHD is caused by pathology in the coronary arteries. This results in myocardial ischaemia which is why the term ischaemic heart disease (IHD) is also used. Right and left coronary arteries carry blood directly from the aorta to the myocardium, the muscle of the heart. CHD most commonly occurs as a result of the deposition of atheroma within the lumen of the coronary arteries. This disease process is termed atherosclerosis. CHD is the most common form of heart disease and is the leading single cause of death in western countries. Heart disease caused by atherosclerosis is less common in developing countries, although if these areas adopt western life styles, the incidence increases. CHD may lead to stable angina pectoris, unstable angina, myocardial infarction, heart failure, dysrhythmias and possible sudden death. Under the age of 65 CHD is less common in women, probably due to the protective effects of oestrogen.
CHAPTER 10 Hypertension - There is no clear agreement on what constitutes hypertension. The World Health Organisation has defined hypertension as a systolic BP over 160 mmHg and a diastolic BP above 90, or both. The International Society of Hypertension of the WHO goes on to define a systolic pressure of 130-139 mmHg and a diastolic of 85-89 mmHg as being ‘high normal’ BP. Others define hypertension as a consistent systolic of over 140 mmHg or a diastolic of over 90 mmHg. The British Hypertension Society considers an optimal BP to be a systolic of less than 120 and a diastolic of less than 80 mmHg. As the risk of hypertensive complications rises progressively with increasing systolic and diastolic pressures, perhaps the best definition of hypertension is ‘that level of blood pressure above which investigation and treatment do more good than harm’. Hypertension may be essential or secondary. In essential hypertension it is not possible to discover a cause of the problem, there is a primary elevation of BP. However, despite there being no clear cause, many factors are known to influence BP and some of these are open to modification. Conversely, acquired or secondary hypertension has an identifiable underlying disorder which causes the elevation in BP. Malignant or accelerated hypertension describes a rapid development of very high blood pressures associated with significant development of complications. Without treatment these patients have a short-term high mortality from stroke, heart or renal failure.
CHAPTER 11 Respiratory Disorders - The cause of pneumonia is usually bacterial infection. While over 100 organisms have been identified as causes of community acquired pneumonia, Streptococcus pneumoniae (often simply called pneumococcus) is the most common. More cases occur in winter and smoking is probably an important risk factor. Patients who are immobile or generally ill are also at greater risk of developing pneumonia. This is a particular risk if patients are nursed lying down, which is why people should be managed sitting up whenever possible. Bacterial pneumonia is also more common in HIV infection compared to the general population.
CHAPTER 12 Hypoxia - When a cell is deprived of oxygen it is no longer able to produce energy using oxygen. When energy is produced using oxygen the process is termed aerobic metabolism. As a hypoxic cell will not be able to use this normal form of metabolism it will start to produce energy in the absence of oxygen, a process called anaerobic metabolism. This will produce lactic acid as a waste product which will reduce the pH of the cell, leading to increased acidity. This acid environment has a damaging effect on the chromosomes, cellular organelles and membranes. As a cell loses its energy supply it is no longer able to pump sodium out of the cell. This means sodium accumulates inside the cell. As sodium is osmotic, water also accumulates within the cells causing them to swell. Despite these changes, cells at this stage have the ability to recover as long as the oxygen supply is restored. However, if the hypoxia persists the damage caused by the acid and swelling will become irreversible. Eventually the membranes around the lysosomes will rupture and the cells will be killed.
CHAPTER 13 Nervous System Disorders - There are two main types of stroke; thromboembolic and haemorrhagic. As the name implies thromboembolic stroke is caused by an occlusion of the normal blood supply by thrombosis or embolism. This cause of stroke is most common accounting for about 85% of cases. Thromboembolic stroke occurs mostly as a compilation of atherosclerosis with atheroma leading to thrombus formation. As in other forms of arterial disease a thrombus will develop on a ruptured plaque of atheroma. The presence of a thrombus will occlude an arterial lumen and so fully or partly cut off the blood supply to an area of the brain. Parts of a thrombus may break away from the main clot generating emboli. When an embolus reaches a vessel, it is too large to pass through, the embolus becomes jammed, occluding blood flow. Thromboembolic pathology may arise from the heart and large extracranial arterial vessels supplying blood to the brain or from smaller intracerebral vessels.
CHAPTER 14 Head Injuries - Injuries to the head which may affect the brain can be caused by any form of trauma such as falls, road traffic accidents or assaults. In practice the terms head injury and brain injury are used synonymously. Primary brain injury describes the damage inflicted on the brain at the time of trauma. This means that when a patient arrives at the point of care the injury already exists. As adult neurones do not have significant mitotic abilities these primary injuries are probably not amenable to treatment.
CHAPTER 15 Endocrine Disorders - In normal physiology the amounts of the various endocrine hormones present in the blood are precisely and homeostatically regulated. However, if a disease process affects an endocrine gland this can result in too much or too little of a particular hormone being secreted into the blood. If too much of a particular endocrine hormone is present in the blood, the target tissue will be overstimulated giving rise to clinical features of hormone toxicity. If however, not enough of a hormone is secreted, the target tissue will be inadequately stimulated giving rise to features of hormone deficiency. For example, if the pituitary gland secreted too much growth hormone during childhood there will be excessive growth, resulting in a giant. Conversely, if not enough growth hormone is produced; the child will fail to grow normally, resulting in a dwarf. Endocrine disorders can affect any of the endocrine glands, but the more common examples discussed in this chapter are those effecting the thyroid and adrenal glands.
CHAPTER 16 Diabetes Mellitus - Two forms of diabetes mellitus are currently recognised, simply referred to as types 1 and 2. Type 1 DM is associated with complete destruction of the beta cells and an absolute insulin deficiency. Type 1 diabetics are always insulin dependent; it is an IDDM (insulin dependent diabetes mellitus). In established cases of type 2 DM there is a reduced level of beta cell function. However, the disease process starts with the insulin receptors; these do not work properly or are reduced in numbers. This means that even though insulin is produced, the receptors are unable to make use of it. This situation is described as insulin resistance. These patients can often be managed without using insulin i.e. type 2 diabetes may be a NIDDM (non-insulin dependent diabetes mellitus). However, type 2 diabetes may progress to become insulin dependent, and so may become an IDDM. Type 2 disease is the most common form of diabetes mellitus.
CHAPTER 17 Disorders of Blood - Anaemia is normally defined as a reduced level of haemoglobin in the blood. Normal blood levels of haemoglobin are 13.5-18g/dL (grams per decilitre i.e. per 100mls of blood) for men and 11.5-16.5g/dL for women. The common feature in all forms of anaemia is a reduced oxygen carrying capacity of the blood. It is important to realise that anaemia is not a diagnosis; the underlying cause of the condition should be identified and treated. Sickle cell disease causes a form of haemolytic anaemia and is associated with numerous other problems; this is why the more general term sickle cell disease is used. In this autosomal recessive condition there is an abnormal form of haemoglobin, called haemoglobin S present in the red cells. When this abnormal haemoglobin deoxygenates, it transforms the erythrocyte into a sickle shape. Initially the sickle shaped cells return to being biconcave discs when they are reoxygenated, but after a few cycles they become rigid and fixed in the sickle position.
CHAPTER 18 Gastrointestinal Disorders – Dysphagia means difficulty in swallowing. Normal swallowing requires the coordination of several muscle groups under precise nervous coordination. Therefore, if the function of muscles or nerves is impaired, as in a stroke, swallowing becomes difficult. Dysphagia may also occur as a result of physical obstruction in the mouth, pharynx or oesophagus. For example, there may be an accumulation of fibrous tissue in the lower oesophagus as a result of peptic acid regurgitation. More ominously, dysphagia may be caused by carcinoma of the oesophagus, obstructing the lumen and preventing the normal passage of food into the stomach.
CHAPTER 19 Disorders of the Liver - Hepatic means to do with the liver. In prehepatic jaundice the abnormality occurs before bilirubin reaches the liver. If there is increased breakdown (that is haemolysis) of red blood cells, bilirubin may enter the blood more rapidly than the liver is able to incorporate it into bile. The result of this is an accumulation of bilirubin in blood and tissue fluids. In this disorder, the excess bilirubin found in the blood is unconjugated, as it has not yet passed through the liver cells. This form of jaundice is usually mild as a healthy liver can excrete up to six times the normal load of bilirubin before the pigment starts to accumulate in the blood. Hepatic (or hepatocellular) jaundice describes jaundice which occurs as a result of disorders affecting the liver cells (i.e. the hepatocytes). Hepatocyte function can be reduced in viral hepatitis (A, B, C, D or E), primary liver cancer or as a result of poisons or drugs. Damaged liver cells are less able to conjugate and transfer bilirubin from the blood into bile. Due to reduced liver cell function conjugated and unconjugated bilirubin therefore accumulates in the blood. In addition to reduced uptake of bilirubin, swelling of the hepatocytes may partly occlude some of the small bile channels, leading to an obstructive component of the jaundice.
CHAPTER 20 Disorders of the Gall Bladder and Bile Ducts - Gallstones (or cholelithiasis) are very common. About 10% of women in their forties have gallstones and this rises to about 30% after the age of 60. The figures for men are about half those for women. Most gallstones (about 75%) are a mixture of cholesterol and bile pigments although pure cholesterol or bile pigment stones also occur. This is most commonly caused by a gallstone obstructing the cystic duct. As bile cannot leave the gall bladder it becomes progressively concentrated as more water is reabsorbed. This highly concentrated bile is very irritating to the lining of the gall bladder leading to a chemically induced cholecystitis. The inflammation also stimulates the formation of pus and the gall bladder becomes distended.
CHAPTER 21 Disorders of the Pancreas - The most common cause of acute pancreatitis in the UK is gallstones. If gallstones are present, the risk of acute pancreatitis is increased by 25 times, in comparison to the general population. It has been suggested that gall stones may block the ampulla, leading to a backlog of pancreatic juice causing increased pressure within the pancreatic ducts. This backlog in turn affects the pancreatic enzyme producing (acinar) cells. These cells contain granules of digestive pre-enzymes called zymogen granules which fuse with lysosomes prematurely activating the pre-enzymes, converting them into active digestive enzymes. Once activated these enzymes will start to digest the cell and will also escape and activate pre-enzymes in adjacent cells. This leads to a chain reaction of digestive enzyme activation. For example, trypsinogen will be converted to trypsin within the cytosol of the cells.
CHAPTER 22 Genitourinary Disorders - Urinary stones (calculi) is a common disorder affecting about 12% of men and 5% of women at some time during their lives. A calculus describes any concretion (a deposit of hard material) which forms in passages which transmit secretions or in cavities associated with secretions. Urinary calculi are often described as ‘stones’. ‘Lith’ or ‘litho’ are prefixes used to describe calculi. Urolithiasis describes the process of stone formation in the urinary tract. Nephrolithiasis literally means kidney stones.
CHAPTER 23 Renal Disorders - Acute Kidney Injury (AKI) was previously termed Acute Renal Failure. In renal failure there is a reduction in glomerular filtration rate (GFR) resulting in a failure of the kidneys to perform their usual excretory function. Glomerular filtrate is normally generated by the process of ultrafiltration that occurs between the glomerular capillaries and Bowman’s space, at the start of the nephron. As a result of a depressed GFR, the kidneys are no longer able to excrete waste products, or maintain homeostasis of water, electrolytes and acid-base balance. Interruption of renal homeostasis can therefore lead to chemical disturbances which are life threatening. This is why AKI is a medical emergency. There may also be a reduction in other renal functions including activation of vitamin D, release of renin and production of erythropoietin.
CHAPTER 24 Alterations in Body Temperature - Pyrexia refers to an increase in body temperature resulting in a fever. A person with a fever is said to be febrile. When the body temperature is not raised the person is described as being apyrexial (the prefix ‘a’ or ‘an’ always means without). It is the hypothalamus which regulates body temperature by comparing the temperature of the blood circulating through the structure with a set point, usually between 36.5-37oC. When blood temperature drops, the hypothalamus initiates mechanisms to increase body temperature; conversely when blood temperature rises above the set point, heat loss mechanisms are initiated. In a fever the set point is increased to a new higher setting.
CHAPTER 25 Wounds and Healing - A wound will heal by primary intention if the edges of the wound can be approximated together. Some form of wound closure is normally employed to keep the wound edges closed. Common ways of achieving closure and stability of the wound edges include adhesive strips, sutures or super glue. Advantages of healing by primary intention include approximation and stabilisation will allow the edges of a wound to heal directly into each other. In primary healing the process is fairly rapid, normally wound edges will be closed with sufficient tensile strength to remove the sutures after7-10 days. However, it takes much longer than this to restore full strength to the wound, even after 2 weeks the wound only has 20% of full strength. If the edges of a wound are closed, the surface area of the wound is reduced. This means that there will be a minimal amount of scar tissue formed, giving good cosmetic and functional results. As the wound is closed, there is less opportunity for secondary colonisation or infection to enter the wound from outside sources of microbiological contamination.
CHAPTER 26 Fractures - A fracture describes any loss of continuity in the substance of a bone; this may range from a hair line crack to massive disruption of a bone. In a closed fracture the skin overlying the break is intact, if there are any injuries to the skin these are superficial and not related to the fracture. In an open (formally called compound) fracture there is a wound connecting the broken ends of the bone with the outside air. In some cases the broken end of bone may protrude through the skin. However, broken ends of bone may penetrate the skin from inside and not be externally visible. This is why even small wounds around a fracture site must be treated with extreme suspicion as they may indicate that a fracture is open. Outside trauma may also cause a wound which is continuous with a fracture. If there is any communication between the broken bone and the surface there is the potential for infection to enter the bone. This may lead to osteomyelitis which can be very difficult to eliminate.
CHAPTER 27 Burns - Burns are a common cause of injury in all countries of the world. Excessive heat is the obvious cause of burns which leads to thermal injuries. These may be caused by flames, steam, hot fluids or hot solids. Unguarded fires are a danger to children and toddlers are at particular risk from kitchen accidents. Older people may be more at risk as a consequence of impaired mobility and poor coordination. In many burn injuries alcohol intoxication is a contributory factor. The severity of a burn depends on the degree of heat and the time a tissue is exposed to the heat source. For example, a temperature of 70OC or more will cause necrosis of the full depth of the epidermis in just a few seconds. Radiation is another possible cause, for example ultraviolet radiation may cause sunburn. Chemical burns may be caused by direct contact with a number of agents. Strong acids such as sulphuric acid from car batteries or alkalis such as cement are frequent causes. Other chemicals such as mustard gas, phosphorus or phenols will also lead to burning. If an electrical current passes through a tissue it will encounter resistance which will lead to heating and development of an electrical burn. If a current passes through the body, deep structures such as bones and muscles may be seriously injured, sometimes despite apparently minor superficial burning.
CHAPTER 28 Pain - Pain has been described as ‘a subjective reaction to an objective stimulus’. Another way of defining pain has been ‘a sensory experience evoked by tissue damage’. However, pain is more complex than a simple cause and effect system, because it involves feelings and emotions as well as sensations. The subjective nature of pain has been well summed up in the now famous McCaffery quote, ‘pain is whatever the experiencing person says it is, existing whenever he or she says it does’. Algesia is another term which means pain. As usual the prefix ‘an’ means without, so analgesia literally means without pain. Treatments which remove or reduce pain are therefore analgesic.